Identification of Novel Genetic Markers and Improved Treatment Options for Diabetic Kidney Disease

Abstract

Diabetic nephropathy, a kidney disease that develops secondary to diabetes mellitus, accounts for most of the reduced life expectancy in individuals with diabetes and is the most common cause of chronic renal failure in developed countries [1]. In its early stages of development, diabetic kidney disease has no symptoms, and is characterized by a reduced glomerular filtration rate and atypical excretion of protein into the urine (i.e., microalbuminuria: 150–300 mg/day). In approximately 20–40% of individuals with diabetes, microalbuminuria progresses to overt nephropathy (urinary protein excretion >300 mg/day) and eventually culminates in end-stage renal disease (ESRD), where renal replacement therapy is necessary to control uremia and other metabolic consequences of kidney failure. ESRD is associated with substantial mortality and economic costs. In the USA alone, mortality rates are approximately 23% per year and nearly 400,000 people receive renal replacement therapy as a result of ESRD, incurring direct medical costs in excess of US$16 billion annually [2]. Unsurprisingly, diabetic kidney disease presents a major public health concern in countries with burgeoning rates of diabetes. At present, there is no cure for diabetic nephropathy; instead, current treatment strategies focus on prevention or delay of disease develop ment and progression. In the early stages of diabetic kidney disease, lifestyle modification (i.e., maintenance of healthy weight, physical activity, dietary restriction of protein, salt and alcohol, avoidance of nonsteroidal anti-inflammatory drugs and smoking cessation), coupled with intensive pharmacological control of glycemia and blood pressure, are prescribed for most patients. However, following